Behavioural, academic and neuropsychological profile of normally gifted Neurofibromatosis type 1 children

In the present study the neuropsychological, academic and social-emotional profiles were examined in Neurofibromatosis type 1 (NF1) children. SUBJECTS: 17 NF1 children (ages 7-11) with NF1 without serious medical problems and with a full scale IQ (FSIQ) above 70. METHODS: Wechsler Intelligence Scale for Children-Revised (WISC-R), academic tests and an exhaustive neuropsychological test battery were administered in all children. Parents and teachers filled out the Child Behavioural Checklist (CBCL) and Teacher Report Form (TRF), respectively, the NF1 children the Experienced Competence Scale for Children (ECSC). RESULTS AND DISCUSSION: Nearly 50% (8/17) of the children showed learning disabilities, when corrected for IQ in the academic evaluations. Isolated impaired literacy skills, particularly spelling problems, were most frequent (4/8), whereas a pure arithmetic learning disability was rare (1/8). Three children presented both learning disabilities. Results on academic and neuropsychological tests did not fit the well-known types of learning disabilities -- nonverbal learning disability (NLD) and dyslexia. Nearly all NF1 children showed visual perceptual and executive dysfunctions. In this study, teachers more frequently reported behavioural problems in NF1 children than parents, as opposed to literature data in a general population. The correspondence of the perception of internalizing problems between the children and teachers was greater than between children and their parents. No correlation was found between the performances on the WISC-R, specific neuropsychological results, academic performances and behavioural problems. The Deficiency in Attention, Motor and Perception (DAMP) concept seems most appropriate in order to describe the neuropsychological deficits and their repercussions on behavioural and academic performances seen in NF1 children.status: publishe

Molecular karyotyping is important in determining the cause of behavioural phenotypes

Background: The cytogenetic delineation and behavioural phenotype of syndromes has evolved from the chromosome level, through FISH (microdeletions syndromes, such as PWS, VCFS, SMS, del1p36) to molecular karyotyping (array CGH). The new syndromes being outlined in recent years account for rarer microdeletions and microduplications, in which the behavioural phenotype is not always well characterized. Method: We have screened by array CGH more than 2000 patients, of which almost 400 have cytogenetic imbalances. We present a subset of these patients, in which the behaviour was an important component of the motivation for molecular karyotyping. Results: Three case studies: 1) A boy with severe feeding problems, speech delay, stereotypic and autistic behaviour. He is dysmorphic and has an intellectual disability. Molecular karyotyping showed a de novo microdeletion of chromosome 15q13.2. 2) A 3-year old girl with difficult behaviour, including negative vocalizations, aggression and repetitive rocking. She has poor weight gain, difficulty in falling asleep and wakes early. She is dysmorphic, has a developmental IQ of 67, a paternally inherited microdeletion of chromosome 9p21.3 and a de novo microduplication of chromosome 17p11.2. 3) A 5-year old girl with intellectual disability who participates in interactive play but remains slow in task execution. Her balance is poor when standing and walking, She does not evidence satiety for food and constantly air-swallows. Molecular karyotyping revealed a de novo microdeletion of chromosome 9qter. Conclusion: The molecular karyotyping results encourage its use in finding the cause of intellectual disability. With the assistance of international collaboration via common databases, such as Decipher, pinpointing and understanding the underlying genes contributing to the overall clinical picture, especially behaviour, will become a reality.status: publishe

Observations on intelligence and behavior in 15 patients with Legius syndrome

Legius syndrome is a RAS-MAPK syndrome characterized by pigmentary findings similar to neurofibromatosis type 1 (NF1), but without tumor complications. Learning difficulties and behavioral problems have been reported to be associated with Legius syndrome, but have not been studied systematically. We investigated intelligence and behavior in 15 patients with Legius syndrome and 7 unaffected family members. We report a mean full-scale IQ of 101.57 in patients with Legius syndrome, which does not differ from the control group. We find a significantly lower Performance IQ in children with Legius syndrome compared to their unaffected family members. Few behavioral problems are present as assessed by the Child Behavior Checklist (CBCL) questionnaire. Our observations suggest that, akin to the milder somatic phenotype, the cognitive phenotype in Legius syndrome is less severe than that of NF1. © 2011 Wiley-Liss, Inc.status: publishe

Emotional and behavioral problems in children and adolescents with neurofibromatosis type 1

To assess emotional and behavioral problems in children and adolescents with neurofibromatosis type 1,parents of 183 individuals aged 10.8 ± 3.1 years (range 6-17) completed the Child Behavior Checklist (CBCL). Also, 173 teachers completed the Teacher's Report Form (TRF), and 88 adolescents (children from 11 to 17 years) completed the Youth Self-Report (YSR). According to parental ratings, 32% scored in the clinical range (above the 90th percentile). This percentage was much lower when rated by teachers or adolescents themselves. Scores from all informants on scales for Somatic complaints, Social problems, and Attention problems were significantly different from normative scores. Attentional problems were associated with lower verbal IQ, male gender, younger age, and ADHD-symptoms. Disease-related factors did not predict behavioral problems scores. Substantial emotional and behavioral problems were reported by parents, teachers, and to a lesser extent by adolescents with NF1 themselves. Possibly, a positive illusory bias affects the observation of behavioral problems by adolescents with NF1.status: publishe

The effect of early life stress on the cognitive phenotype of children with an extra X chromosome (47,XXY/47,XXX)

Studies on gene–environment interactions suggest that some individuals may be more susceptible to life adversities than others due to their genetic profile. This study assesses whether or not children with an extra X chromosome are more vulnerable to the negative impact of early life stress on cognitive functioning than typically-developing children.A total of 50 children with an extra X chromosome and 103 non-clinical controls aged 9 to 18 years participated in the study. Cognitive functioning in domains of language, social cognition and executive functioning were assessed. Early life stress was measured with the Questionnaire of Life Events. High levels of early life stress were found to be associated with compromised executive functioning in the areas of mental flexibility and inhibitory control, irrespective of group membership. In contrast, the children with an extra X chromosome were found to be disproportionally vulnerable to deficits in social cognition on top of executive dysfunction, as compared to typically-developing children. Within the extra X group the number of negative life events is significantly correlated with more problems in inhibition, mental flexibility and social cognition. It is concluded that children with an extra X chromosome are vulnerable to adverse life events, with social cognition being particularly impacted in addition to the negative effects on executive functioning. The findings that developmental outcome is codependent on early environmental factors in genetically vulnerable children also underscores opportunities for training and support to positively influence the course of development.Development Psychopathology in context: clinical setting